6,7-dichloro-2-methylthio-1-(β-D-ribofuranosyl)naphtho[2,3-d]imidazole | 285132-12-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 苯并咪唑核糖核苷和核糖核苷酸
• 英文名称: 6,7-dichloro-2-methylthio-1-(β-D-ribofuranosyl)naphtho[2,3-d]imidazole
• 英文别名: (2R,3R,4S,5R)-2-(6,7-dichloro-2-methylsulfanylbenzo[f]benzimidazol-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 285132-12-9
• 化学式: C₁₇H₁₆Cl₂N₂O₄S
• 分子量: 415.297
• InChiKey: RMZSZSDHPFFJGB-KLHDSHLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6,7-dichloro-2-methylthio-1-(β-D-ribofuranosyl)naphtho[2,3-d]imidazole 在 Raney-Ni W₄ 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 3.5h， 以52%的产率得到6,7-dichloro-1-(β-D-ribofuranosyl)naphtho[2,3-d]imidazole
  参考文献：
  名称：

  三环核苷（尺寸探针）作为某些抗病毒多卤代苯并咪唑核糖核苷类似物的设计，合成和生物学评估。

  摘要：

  在我们的实验室中合成了多卤代苯并咪唑核苷2,5、6-三氯-1-（β-D-呋喃呋喃糖基）苯并咪唑（TCRB）和2-溴类似物（BDCRB），并将其作为人巨细胞病毒的有效和选择性抑制剂（ HCMV）具有新颖的作用方式。为了研究关键亚结构的行为，在尺寸上扩展并探究目标酶的空间限制，一系列了2-取代的6、7-二氯-1-（β-D-呋喃呋喃糖基）制备了萘酚，2,3-二咪唑和2-取代的6,7-二氯咪唑-4、5-喹啉的N1-和N3-核糖核苷。核苷6、7-二氯-1-（β-D-呋喃呋喃糖基）咪唑4,5-bquinolin-2-one和6,7-二氯-3-（β-D-核呋喃糖基）咪唑-4,5-选择了bquinolin-2-one，并将其用作咪唑4的关键合成中间体，5-喹啉系列。对化合物针对HCMV和1型单纯疱疹病毒的活性进行评估后发现，TCRB的三氯类似物（2a，3a）对HCMV的活性与TCRB几乎相同，但具有更高的

  DOI：

  10.1021/jm990290y
• 作为产物：
  描述：

  1-乙酰氧基-2,3,5-三苯甲酰氧基-1-beta-D-呋喃核糖 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 甲醇 为溶剂， 反应 24.5h， 生成 6,7-dichloro-2-methylthio-1-(β-D-ribofuranosyl)naphtho[2,3-d]imidazole
  参考文献：
  名称：

  Synthesis of 2,6,7-Trichloro-1-(β-d-ribofuranosyl)naphtho[2,3-d]imidazole:  A Linear Dimensional Analogue of the Antiviral Agent TCRB

  摘要：

  Human cytomegalovirus (HCMV) remains a significant clinical problem in neonates and immunocompromised individuals such as those undergoing transplantation as well as individuals with acquired immune deficiency syndrome (AIDS). Recently in our laboratory, 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB, 1a) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB, 1b) were found to have better activities in cell culture studies against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole compounds appear to act by a unique mechanism. However, as the biological target of TCRB and BDCRB has not been completely identified, 2,6,7-trichloro-1-(beta-D-ribofuranosyl)naphthol[2,3-d]imidazole (2) was designed as a linear dimensional analogue of TCRB for a study on the spatial limitation of the binding site in the target enzyme. In the synthesis, a convenient route was developed for the synthesis of 2-substituted 6,7-dichloronaphtho[2,3-d]imidazoles involving a Diels-Alder reaction of 4,5-dichloro-o-quinodimethane (8) as the key step. 6,7-Dichloro-1,4-dihydro-2,3-benzoxathiin 3-oxide (15) was found to be an ideal precursor for the generation of the elusive intermediate 8. The ribosylation of 6,7-dichloronaphtho[2,3-d]imidazoles was influenced by the functional group at the 2-position and 6,7-dichloro-2-methylthionaphtho[2,3-d]imidazole (3c) was found to smoothly undergo ribosylation. The 2-methylthio group of the unprotected nucleoside 25 was converted into a chloro group under mild conditions to give nucleoside 2 in high yield.

  DOI：

  10.1021/jo971152o

文献信息

• Design, Synthesis, and Biological Evaluation of Tricyclic Nucleosides (Dimensional Probes) as Analogues of Certain Antiviral Polyhalogenated Benzimidazole Ribonucleosides
  作者：Zhijian Zhu、Blaise Lippa、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm990290y

  日期：2000.6.1

  The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behavior of the key substructure in a dimensionally extended manner and probe the spatial

  在我们的实验室中合成了多卤代苯并咪唑核苷2,5、6-三氯-1-（β-D-呋喃呋喃糖基）苯并咪唑（TCRB）和2-溴类似物（BDCRB），并将其作为人巨细胞病毒的有效和选择性抑制剂（ HCMV）具有新颖的作用方式。为了研究关键亚结构的行为，在尺寸上扩展并探究目标酶的空间限制，一系列了2-取代的6、7-二氯-1-（β-D-呋喃呋喃糖基）制备了萘酚，2,3-二咪唑和2-取代的6,7-二氯咪唑-4、5-喹啉的N1-和N3-核糖核苷。核苷6、7-二氯-1-（β-D-呋喃呋喃糖基）咪唑4,5-bquinolin-2-one和6,7-二氯-3-（β-D-核呋喃糖基）咪唑-4,5-选择了bquinolin-2-one，并将其用作咪唑4的关键合成中间体，5-喹啉系列。对化合物针对HCMV和1型单纯疱疹病毒的活性进行评估后发现，TCRB的三氯类似物（2a，3a）对HCMV的活性与TCRB几乎相同，但具有更高的
• Synthesis of 2,6,7-Trichloro-1-(β-<scp>d</scp>-ribofuranosyl)naphtho[2,3-<i>d</i>]imidazole:  A Linear Dimensional Analogue of the Antiviral Agent TCRB
  作者：Zhijian Zhu、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jo971152o

  日期：1998.2.1

  Human cytomegalovirus (HCMV) remains a significant clinical problem in neonates and immunocompromised individuals such as those undergoing transplantation as well as individuals with acquired immune deficiency syndrome (AIDS). Recently in our laboratory, 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB, 1a) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB, 1b) were found to have better activities in cell culture studies against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole compounds appear to act by a unique mechanism. However, as the biological target of TCRB and BDCRB has not been completely identified, 2,6,7-trichloro-1-(beta-D-ribofuranosyl)naphthol[2,3-d]imidazole (2) was designed as a linear dimensional analogue of TCRB for a study on the spatial limitation of the binding site in the target enzyme. In the synthesis, a convenient route was developed for the synthesis of 2-substituted 6,7-dichloronaphtho[2,3-d]imidazoles involving a Diels-Alder reaction of 4,5-dichloro-o-quinodimethane (8) as the key step. 6,7-Dichloro-1,4-dihydro-2,3-benzoxathiin 3-oxide (15) was found to be an ideal precursor for the generation of the elusive intermediate 8. The ribosylation of 6,7-dichloronaphtho[2,3-d]imidazoles was influenced by the functional group at the 2-position and 6,7-dichloro-2-methylthionaphtho[2,3-d]imidazole (3c) was found to smoothly undergo ribosylation. The 2-methylthio group of the unprotected nucleoside 25 was converted into a chloro group under mild conditions to give nucleoside 2 in high yield.